Chronic refractory, or non-healing, wounds or ulcerations of the extremities represent a major medical condition affecting millions of patients. A chronic wound is defined as a wound that does not show signs of significant healing, or progresses, after use of topical/surgical treatment measures for six months. Non-healing wounds affect 6.5 million patients, affecting nearly 2% of the U.S. population, with an annual cost to the healthcare system of $25 billion. These numbers are rising with the aging population and the increasing incidence of diabetes, a leading cause of refractory leg ulcers. Other common causes of chronic wounds include venous stasis ulcers, and decubitus ulcers which develop in immobilized patients. Current treatments for extremity (diabetic, venous stasis) or decubitus ulcers often do not produce sustained or complete healing. Among diabetics, over half of ulcers recur within three years, and 15% ultimately require amputations, with significant consequent disability. New therapeutic agents that promote complete wound closure are needed for this enormous health burden. The Principal Investigators have identified a drug (Arginine Butyrate, AB) which, when given parenterally, dramatically accelerates healing, including complete healing in a highly-refractory chronic wound population, sickle cell leg ulcers, [which heal 10-20 times more slowly than comparable decubitus or diabetic ulcers]. The parenterally-delivered drug had a benign safety profile. Although parenteral (IV) delivery via indwelling port devices was acceptable for the extremely severe population studied in the prior clinical trial, a topical delivery system would offer many feasibility advantages for broader application and not require delivery primarily in clinical facilities. Phoenicia Biosciences has developed an innovative prototype topical spray delivery system of the same drug. This first-in-class therapeutic should provide a highly significant impact on the suffering and economic burden imposed by the growing health care problem of chronic wounds. The Aims of this Phase I application are: (I) Develop a new topical dendrimer hydrogel spray preparation of AB, and test the activity of the new topical preparation in two animal models of wound healing (a chronic wound healing model and diabetic chronic wound healing model); (II.) Perform CMC studies required for a new IND of the novel topical formulation of Arginine Butyrate. These IND enabling studies will allow this new therapeutic to be tested in clinical trials.